More and more psychedelic drugs, such as LSD and ecstasy, are being tested to treat mental health issues, such as anxiety, depression and post-traumatic stress disorder. But very little is known about the mechanism by which these substances exert their beneficial effects. A team of researchers from McGill University and the Italian universities Vita-Salute San Raffaele and Padua has just shed light on how LSD manages to relieve mice who have become anxious due to the stress imposed on them.
Already in 2015, the DD Gabriella Gobbi, a professor and researcher in psychopharmacology in the Department of Psychiatry at McGill University, found that at low doses, LSD acts on serotonin, a neurotransmitter that is involved in anxiety and depression. More recently, with her team from the Research Institute of the MUHC and Italian colleagues, she studied the effect of this hallucinogenic drug on anxiety and she discovered that LSD borrows the same mechanism of action as antidepressants. commonly used to treat depression and generalized anxiety, such as Prozac, Zoloft, Cipralex, to induce its anxiolytic effect.
These researchers were able to demonstrate that, just as antidepressants belonging to the class of selective serotonin reuptake inhibitors do, LSD increases the release of serotonin from neurons in the brain when administered in small doses for seven days. in a row to mice exposed to chronic stress conditions.
The scientists also noticed that this same administration favored the formation of new “dendritic spines” – small growths on the surface of dendrites, these extensions from the cell body of neurons – at the level of the hippocampus and the prefrontal cortex. These two regions of the brain are involved in depression and anxiety.
“The genesis of dendritic spines makes it possible to establish new synapses and thus increases the number of connections between neurons. The increase in the number of dendritic spines is an indirect sign of the increase in neuronal plasticity that is induced by LSD and antidepressants,” explains Dr.D Gobbi. She points out that there is a decrease in neuroplasticity in depression and other mental health problems.
The increase in neuronal transmission ensured by serotonin as well as the creation of new synapses and connections would therefore be at the origin of the beneficial effects observed in mice treated with LSD, as described in an article published Thursday in the journal Neuropsychopharmacology. The administration of this substance for seven days in a row has in fact significantly reduced stress, as well as the anxiety which results from it, in mice. It also had a positive effect on the social behavior of the mice, which spent more time together and interacted more with each other.
Like antidepressants
A few clinical studies aimed at experimenting with the curative use of psychedelic substances have been carried out in humans. In one of them, the prolonged administration of antidepressants was compared to that of psilocybin (the active component of magic mushrooms) for two days. Both protocols had the same efficacy, which also proved to be durable over time.
“What emerges from clinical studies in humans is that psychedelic drugs cannot be used every day, like Prozac. They should only be given in small doses for a few days only. But such an administration would have a long-term effect, ”underlines the DD Gobbi.
Would these hallucinogenic substances therefore have an advantage over antidepressants? It will be necessary to carry out even more studies to confirm it, nuances the researcher.
[Chez l’humain]psychedelic drugs cannot be used every day, such as Prozac
Psychedelic drugs, on the other hand, have significant side effects if used in too high doses. They can cause psychosis, dissociation, and most importantly, they can have some long-term neurotoxic effects.
The DD Gobbi insists that these substances should be taken under the supervision of a doctor or therapist. “As they can induce dissociation, it is essential that a therapist accompanies the person through this dissociation which can nevertheless prove to be beneficial. Because this dissociation can allow the patient to see himself with a distance, to understand his suffering, even to give meaning to his suffering. But we do not yet know if the dissociation is important, if it is part of the healing process or if it is an undesirable side effect, ”explains the psychiatrist.
“We do not yet know the appropriate dose of LSD that should be chosen to be administered in the clinic. We need to determine this dose, the duration of administration and the precise clinical applications”, underlines the DD Gobbi, who is currently applying for authorization to conduct a clinical study here in Montreal that would help answer these questions.
The scientist believes that we will know, in the next five years, if the use of psilocybin and LSD is possible and safe in a clinical context.